Sub-aggregatory doses of catecholamines prevent prostacyclin-induced inhibition of platelet aggregation

Abstract

To assess the effect of subaggregatory concentrations of catecholamines on the antiaggregatory effect of prostacyclin (PGI 2), platelets from normal human volunteers were exposed sequentially in vitro to epinephrine (≤50 nM) or norepinephrine (≤1 μM) followed by PGI 2 and adenosine diphosphate (ADP). Platelets thus pretreated did not manifest the normal inhibitory response to PGI 2, aggregating to a similar extent as platelets exposed to ADP alone. This effect was unaffected by aspirin but was abolished by exposure to phentolamine. Catecholamine pretreatment similarly blocked the PGI 2-induced increase in intracellular cyclic AMP, an effect which was also reversed by phentolamine. These data suggest that platelets exposed in vivo to elevated catecholamine concentrations, such as are seen clinically during myocardial infarction, might be similarly unresponsive to endogenous PGI 2.